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In 2003 after 13 years of global collaboration, the Human Genome Project was successfully completed, providing a comprehensive blueprint of human genetic information. This has given impetus to a rapidly expanding level of research in disease diagnosis, such as cancer, personalized medical treatments, the understanding of genetic disorders, genetic engineering therapies, and applications in tissue engineering, epigenomics, molecular and cell biology, as well as forensic science. In addition, it has raised ethical, legal and social questions about how we use genetic information.
So how does this recent understanding about our genes impact the research and development of fiber-based textile structures? In this article we provide three examples of current advances in biomedical textiles at the Wilson College of Textiles, North Carolina State University (NCSU), that have been inspired and promoted by the growing interest in improving healthcare outcomes for patients, clinicians, healthcare professionals and the medical device industry. It is also worth noting that these three examples illustrate the diversity of biomedical textile products and our innovative ideas.
Targeted drug delivery
The first project involves the targeted delivery of the chemotherapeutic drug, doxorubicin, to treat a particularly aggressive abdominal cancer called desmoplastic small round cell tumor (DSRCT). These sarcomas, characterized by a poor prognosis due to late diagnosis, rapid progression, and resistance to conventional therapies, predominantly affect young males, with a median age at diagnosis of 22 years.
Despite undergoing aggressive treatment, the outlook remains bleak, with a very low five-year-survival rate. Current treatment protocols typically involve surgical removal of the tumor, followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy, which can lead to significant toxic side effects and limit the maximum achievable therapeutic dose. The presence of residual cancer cells or micro-metastases after surgery considerably heightens the risk of cancer recurrence, emphasizing the urgent need for effective postoperative monitoring and treatment strategies.
We are developing an implantable, resorbable mesh designed to be placed at the tumor site following surgery to eliminate any residual cancer cells. The mesh is made from poly(lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer that is FDA-approved for drug delivery applications. It is produced using a specialized braiding technique that results in a flexible, porous tubular structure, providing essential mechanical support to the surgical site.
This structure is coated with a resorbable hydrogel containing the doxorubicin (see figure 1). As the PLGA polymer undergoes hydrolytic degradation, it breaks down into lactic and glycolic acids, which are naturally metabolized by the body and avoids the need for surgical removal. The hydrogel coating enables a sustained release of the doxorubicin over a period of two weeks, which is crucial during the postoperative window before scar tissue formation begins to hinder drug delivery. This localized delivery system effectively maintains therapeutic drug concentrations at the tumor site while minimizing systemic exposure and associated toxicity.
Elution studies have demonstrated a sustained release profile for the doxorubicin over 21 days, with more than 80 percent of the drug being released within the initial two weeks, which coincides with the critical postoperative period. Degradation studies indicated that the mesh maintains its structural integrity for three weeks before gradually undergoing surface erosion, effectively balancing mechanical support with resorption timelines.
Initial in vivo studies conducted on immunocompromised mice have demonstrated that both the blank PLGA mesh and the hydrogel are non-inflammatory, biocompatible and safe for implantation. We are currently optimizing the implant to improve its mechanical properties, drug release kinetics, and ease of surgical placement.
Upcoming in vitro assays utilizing primary DSRCT cells will assess the timing of cancer cell death, DNA damage, and the inhibition of cell proliferation. In vivo studies will focus on evaluating tumor reduction and recurrence rates. Early data indicate that this system could significantly decrease recurrence by targeting the residual tumor cells before forming a stromal barrier layer.
To advance this technology, collaboration with surgeons and industry partners is crucial. Input from surgeons will enhance the design of the mesh to allow for customizable sizes and shapes, aid in the implantation process and validate its efficacy in preclinical trials. Obtaining regulatory approval will involve conducting toxicity studies in a larger animal model and undertaking Phase I trials to establish safety for human use.
For successful commercialization, collaborations with biotech firms specializing in drug-eluting devices will significantly accelerate clinical adoption. Furthermore, adapting this platform for other peritoneal cancers, such as ovarian or gastric cancers, will expand its market potential.
Composite scaffolds
The second project involves the development of three-dimensional fiber-foam composite scaffolds for skin tissue engineering. Skin injuries, such as burns, chronic wounds, abdominal fistulas and diabetic ulcers, traumatic injuries, and genetic defects are a significant clinical challenge with limited treatment options.
Treatment failure can lead to infections and life-threatening complications. Autografts, which involve taking the patient’s own tissue, and synthetic skin substitutes have limitations such as donor site morbidity, poor integration, and inadequate mechanical properties. So, there is a pressing need for advanced biomaterials that can promote effective skin regeneration.
Our approach is to develop 3D foam-fiber composite scaffolds that mimic the structural and mechanical properties of native skin tissue. The bioresorbable polymer foam matrix is formed around a particle fusion and porogen leaching technique that controls the pore size distribution and the pore interconnectivity. In fact, the porogen particles can be separated into different sizes to create a precisely controlled pore size gradient through the thickness of the scaffold.
Fibers or yarns are added as dispersed staple or full-length oriented layers within the foam to adapt to various skin types, thicknesses and anatomical locations. The resulting 3D foam-fiber composites can then be surface coated with collagen or gelatin to improve cell compatibility.
Our current work achieves all of the aspects described above, using a repeatable and scalable manufacturing process. Individual parameters such as fiber type, pore size distribution, overall dimensions and type of foam matrix can be selected and combined to build the desired foam-fiber composite structure. These structures have superior mechanical properties compared to unreinforced foams and also provide excellent surfaces for cell migration, adhesion and proliferation.
Figure 2 shows examples of foams that are 5 – 10 mm thick, reinforced either with full-length silk and synthetic sutures, or with collagen, PGLA, and polyglycolide based Glycoprene™ yarns. Figure 3 shows SEM images of fiber-reinforced foams with and without cells.
These 3D foam-fiber composite scaffolds combine the advantages of different materials and different structures. The fabrication method we have developed allows independent selection of the type of reinforcing fiber or yarn, the fiber or yarn density and orientation, integrated within a polymer foam with a specific architecture. This approach allows us to replicate the complex architecture of natural skin tissue, thereby improving the potential for successful skin tissue regeneration and function.
To develop this technology further and achieve commercial manufacturing production levels, it will be necessary to scale-up the fabrication process. This will involve the development of improved tooling for the porogen fusion process and the polymer infusion and foam formation steps.
In addition, animal testing will be necessary to determine the biocompatibility and durability as well as the selection of the optimal composite structure and degradation rate in an in vivo environment. These data will be required by the Food and Drug Administration (FDA) for inclusion in their Class 2 regulatory approval submission.
Barbed surgical sutures
The third project involves the development of a special type of barbed or knotless surgical suture that is used by plastic and cosmetic surgeons to improve their patients’ visual appearance. The title of the project is “Ultrashort pulse laser fabrication and evaluation of innovative resorbable barbed sutures”.
According to the American Society for Plastic Surgery 2020 annual report, there are about 23 million plastic reconstructive surgical procedures performed in the US each year and the number is growing exponentially worldwide. To achieve better surgical outcomes, plastic surgeons are transitioning from a conventional knotted monofilament and braided surgical suture to a novel knotless suture, known as a barbed suture. These barbed sutures have a plurality of barbs cut at specific intervals as projections around the periphery of the main filament (Figure 4. See also video below.)
Currently these barbed sutures are manufactured mechanically using a straight metal blade with the same standard barb dimensions and geometry. However, our previous studies have shown that the same barb cut depth and cut angle are not suitable for all surgical procedures. The anchoring performance of a barbed suture varies depending on the surrounding tissue, the anatomical site and the particular surgical procedure.
In our experimental study, barbed sutures were fabricated in various shapes and geometries using a femtosecond laser, which is an ultrashort pulse laser system. Both straight and curved barbs were fabricated on resorbable catgut, and synthetic biomaterial monofilaments, such as poly (4-hydroxybutyrate).
It was observed from the results that the femtosecond laser system was able to fabricate both straight and curved barbs consistently with similar mechanical properties and anchoring behavior to those barbed sutures cut mechanically with a blade. In fact, the laser cut barbs were more reproducible and had improved precision compared to the mechanically cut barbs. An evaluation of the thermal behavior and degradation profile of the barbed sutures confirmed that the femtosecond laser system had a negligible effect on the integrity of the polymeric material.
Our study on the laser fabrication of barbed sutures shows a promising direction for the commercial scale-up of barbed suture manufacture. This answers the question of how to commercially fabricate barbed sutures with different barb geometries to meet the requirements of different clinical applications and surgical procedures.
Currently we are in discussion Dr. Adam Summers MD, a plastic surgeon in Baltimore, Maryland, who is considering licensing this technology for the fabrication of polypropylene barbed sutures as a component in his novel surgical device. This initiative of moving laser fabrication into commercial production and clinical practice will open up new possibilities for the use of barbed sutures in different surgical procedures.
Essential for success
In this article we have seen three examples of using textile technology to improve the design and functionality of medical textile products for surgical and healthcare applications. The research and development process continues to make innovative advances, often by working in an interdisciplinary field, bringing different technologies together for the first time. It is important to note that there are two essential ingredients in converting a novel idea into a viable commercial clinical or healthcare product, and they are:
- A clinician, surgeon or healthcare professional who sees merit in the invention and who is prepared to be an ambassador to promote its clinical use.
- A business or corporate entity that is prepared to collaborate with you to ensure that the scale-up and launch is feasible from a technical, legal, commercial, promotional and sales, and marketing point of view.
For each of the three examples included in this article, we, at the Wilson College of Textiles, continue to seek and include both of these ingredients as the research and development process advances through the experimental stages of prototyping, in vitro evaluation and in vivo animal trials.
The co-authors are, or have been, members of the Biomedical Textiles (BMT) Research Group at the Wilson College of Textiles, North Carolina State University. Dr. Martin King is professor of Biotextiles and Textile Technology and a Fellow of the Institute of Textile Science in Canada and an Associate (Chartered Engineer) of the Textile Institute in the U.K. Dr. Mengnan Dennis (Fiber/Foam composites) is a post-doctoral fellow working in the BMT research group. Dr. Karuna Nambi Gowri (Barbed sutures) is a post-doctoral Scholar in Department of Forest Biomaterials, NCSU College of Natural Resources with Dr Joel Pawlak. Ummay Nisha Jahan (Targeted drug delivery for cancer) is a Ph.D. graduate student working with Dr. Andrea Hayes-Dixon, MD, Pediatric oncology surgeon at Howard University. Each co-author created their own images as part of their research project.